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β2-肾上腺素能受体的多态性与夜间哮喘及特布他林雾化剂的反应相关。

Polymorphisms of the β2-adrenergic receptor correlated to nocturnal asthma and the response of terbutaline nebulizer.

机构信息

Department of Pediatrics, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.

出版信息

Pediatr Neonatol. 2011 Feb;52(1):18-23. doi: 10.1016/j.pedneo.2010.12.011. Epub 2011 Feb 23.

Abstract

BACKGROUND

Inhaled β(2)-adrenergic receptor (β(2)-AR) agonists are the mainstay of treatment of acute asthma. Polymorphisms of the β(2)-AR, especially codons 16, 27, and 164, may affect the functions of the receptor. This study was conducted to investigate whether different polymorphisms of the β(2)-AR are related to the treatment responses of an inhaled β(2)-AR agonist in children with nocturnal and nonnocturnal asthma in Taiwan.

METHODS

The nocturnal asthma group consisted of 27 children (mean age of 10.3±2.4 years), and the nonnocturnal asthma group consisted of 24 patients (mean age of 9.9±3.0 years). Allele-specific polymerase chain reaction was performed to determine 16, 27, and 164 loci alleles of β(2)-AR genetic polymorphisms, and peak expiratory flow (PEF) was measured before and 1 hour after inhalation of 0.2mg/kg/dose of terbutaline to determine the treatment response in these patients.

RESULTS

The polymorphisms of β(2)-AR 27 but not 16 or 164 were significantly associated with the response to terbutaline nebulizer (p<0.05). The polymorphism of β(2)-AR 16 was associated with nocturnal asthma (p=0.027). The Gly16 allele was more prevalent in the nocturnal asthma group (9/27; 33.3%) than in the nonnocturnal asthma group (3/24; 12.5%). Arg16 allele was less prevalent in the nocturnal asthma (3/27; 11.1%) than in the nonnocturnal asthma group (10/24; 41.7%). There was also a linkage disequilibrium found between β(2)-AR 16 (Arg/Arg) and β(2)-AR 27 (Gln/Gln).

CONCLUSION

These findings suggest that polymorphisms of β(2)-AR 16 are related to nocturnal asthma and polymorphisms of β(2)-AR 27 are associated with the variable responses to the inhaled terbutaline in children with nocturnal and nonnocturnal asthma.

摘要

背景

吸入性β(2)-肾上腺素受体(β(2)-AR)激动剂是治疗急性哮喘的主要方法。β(2)-AR 的多态性,特别是密码子 16、27 和 164,可能影响受体的功能。本研究旨在探讨β(2)-AR 的不同多态性是否与台湾地区儿童夜间和非夜间哮喘患者吸入β(2)-AR 激动剂的治疗反应有关。

方法

夜间哮喘组由 27 名儿童(平均年龄 10.3±2.4 岁)组成,非夜间哮喘组由 24 名患者(平均年龄 9.9±3.0 岁)组成。采用等位基因特异性聚合酶链反应检测β(2)-AR 遗传多态性的 16、27 和 164 位等位基因,吸入 0.2mg/kg/剂量特布他林后 1 小时测量呼气峰流速(PEF),以确定这些患者的治疗反应。

结果

β(2)-AR27 但不是 16 或 164 的多态性与特布他林雾化器的反应显著相关(p<0.05)。β(2)-AR16 的多态性与夜间哮喘有关(p=0.027)。Gly16 等位基因在夜间哮喘组(9/27;33.3%)中比非夜间哮喘组(3/24;12.5%)更常见。Arg16 等位基因在夜间哮喘组(3/27;11.1%)中比非夜间哮喘组(10/24;41.7%)更少见。还发现β(2)-AR16(Arg/Arg)和β(2)-AR27(Gln/Gln)之间存在连锁不平衡。

结论

这些发现表明,β(2)-AR16 的多态性与夜间哮喘有关,β(2)-AR27 的多态性与夜间和非夜间哮喘儿童吸入特布他林的可变反应有关。

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